J Korean Soc Food Sci Nutr 한국식품영양과학회지 43(1), 4~46(214) http://dx.doi.org/1.3746/jkfn.214.43.1.4 지방간모델에서가시오가피발효물의간기능개선효과 조주현 1 박인재 1 최수영 2 백순옥 1 김충식 1 1 휴럼중앙연구소 2 충북대학교생물학과 The Hepatoprotective Effect of Acanthopanax senticosus Fermentation Products in Fatty Liver Model Ju-Hyun Cho 1, In-Jae Park 1, Soo-Young Choi 2, Soon-Ok Baik 1, and Choong-Sik Kim 1 1 Hurum Central Research Institute Co., Ltd., Chungbuk 363-883, Korea 2 College of Biology, Chungbuk National University, Chungbuk 361-763, Korea ABSTRACT We demonstrated that Acanthopanax senticosus fermentation products (FM-5111 and FM-5131) administered to rats functionally protect against DL-ethionine-induced and ethanol-induced fatty liver models. In DL-ethionine-induced fatty liver models, the serum concentrations of aspartate aminotransferase (AST), as well as liver concentrations of triglyceride and total lipid against the control decreased in FM-5111 and FM-5131 treated rats. In ethanol-induced fatty liver models, FM-5111 and FM-5131 treated rats showed a decrease in the liver concentrations of triglyceride and total lipid in ethanol-induced fatty liver models. There were no significant differences in the serum concentrations of AST and alanine aminotransferase in FM-5111 and FM-5131 treated rats. Additionally, FM-5111-, or FM-5131- treated rats showed no significant differences in the body weight gain between the control. These results indicate that Acanthopanax senticosus fermentation products might have protective effects against DL-ethionine-induced and ethanol-induced fatty liver models. Key words: Acanthopanax senticosus fermentation, DL-ethionine-induced fatty liver model, ethanol-induced fatty liver model, Ganoderma lucidum, Phellinus linteus 서 최근식생활의변화등으로인하여간질환환자가늘고있다. 이는최근우리나라경제성장과생활수준의향상으로인하여칼로리섭취가증가하였으나활동적인운동의기회가감소하여여분의칼로리가지방의형태로피하지방층이나간에축적되어비만과 steatosis(simple fatty liver), NASH(nonalcoholic steatohepatitis; hepatitis, fibrosis), cirrhosis(irreversible) 등과같은비알코올성지방간이증가하였기때문이다 (1,2). 이와더불어알코올섭취증가로인한알코올성지방간또한가장흔히발생하는간질환의예이다 (3). 지방간이란지방의과도한섭취, 간내축적및합성증가 (4), 간장내저장지방증가및간장으로부터말초조직으로이동하는지방의감소, 배출감소등이원인이되어 (2,5) 정상적인지방대사가이루어지지못하여지방이전체간무게의 5% 이상을차지하게되는경우를말한다 (2). 론 Received 1 September 213; Accepted 17 October 213 Corresponding author. E-mail: dusvnd68@hurum.co.kr, Phone: +82-43-217-177 만성적인에탄올섭취는신체의주요기관에치명적인영향을미칠수있으며 (6), 지방산합성과분비및대사에중요한역할을담당하는간세포에장애를초래하고간비대화, 간괴사, 알코올성간염, 지방간및간경변등으로진전된다 (6,7). 만성적인알코올섭취에의해서뿐만아니라고용량을 1회섭취하는것만으로도알코올성지방간이유도될수있다 (8). 비알코올성지방간질환 (nonalcoholic fatty liver disease, NAFLD) 은알코올섭취가거의없는사람에서나타나며, 특별한임상적의의가없는단순한지방간부터간경화를일으키는더심한형태의비알코올성지방간염 (NASH) 에이르는다양한범위의간질환을포함한다 (9). 근래에들어전세계적으로비만, 당뇨, 고혈압, 고지혈증등대사성증후군의유병률이증가하면서비알코올성지방간의유병률도증가됨에따라임상적으로많은관심을끌고있다 (1-13). 가시오가피에대한생리활성및약리효능연구는 Brekhman(14) 과 Ovodov 등 (15) 에의해러시아산가시오가피에서분리한 eleutheroside류가항피로작용과항스트레스작용을갖고있음이과학적으로입증된이후로생체기관의기능증대, 중추신경흥분작용, 근육운동촉진작용, 대사촉
지방간모델에서가시오가피발효물의간기능개선효과 41 진작용, 동맥혈압의정상화, 항염작용, 항암작용, alloxane 유발, 항당뇨작용, 해독작용, 항류마티스등다양한생리적작용에관하여보고되고있다 (16,17). 영지버섯 (Ganderma lucidum) 은담자균류의다공균과에속하는버섯으로이뇨, 강장, 면역, 항암등의치료제로서이용되고있으며 (18-2), 영지버섯에대한항암작용, 면역증강작용, 항알레르기작용, 항고혈압작용, 고지혈증개선및혈당강하작용등에대해보고되어있다 (21-24). 상황버섯 (Phellinus linteus) 은소화기계통의암인위암, 식도암, 십이지장암, 결장암, 직장암, 간암의절제수술후화학요법을병행할때면역기능을증강시키며, 자궁출혈및대하, 월경불순, 장출혈, 오장및위장기능을활성화시키는작용과해독작용이있다고알려졌다 (2). 본연구는가시오가피를천연배지로영지버섯균사체와상황버섯균사체를각각배양하여발효물을제조하였고, DL-ethionine과 ethanol로지방간이유발된 rats에가시오가피발효물추출물을농도별로투여하여간기능개선에대한효과를분석하였다. 재료및방법가시오가피발효물생산및추출가시오가피-영지버섯발효물은가시오가피줄기와잎의비율을 8 : 2으로혼합하였고, 가시오가피-상황버섯발효물은가시오가피의줄기와잎의비율이 : 으로혼합하여천연배지원료를준비하였다. 영지버섯 (Ganoderma lucidum; KCTC 6729) 과상황버섯 (Phellinus linteus; KCTC 6719) 종균제조는 potato dextrose agar(difco, Franklin Lakes, NJ, USA) 배지에접종하고 28 C에서 7일간배양한후, cork borer(φ 8 mm) 로절취하여멸균된 potato dextrose broth(difco) 배지가 1 ml씩분주되어있는삼각플라스크에 5~6개의절취된균주디스크를접종하고 6일간진탕배양 (SI-4R, JEIOTECH, Seoul, Korea) 한다음분쇄기 (Waring, Winchester, CT, USA) 로균질화한후 potato dextrose broth 배지가 1 ml씩분주되어있는삼각플라스크에 9 ml를접종한후 5일간배양하여종균으로사용하였다. 천연배지원료를수분이 63±3% 가되도록정제수를투입하고 autoclave(jeio tech, Daejeon, Korea) 에서 121 C, 2분간초벌멸균한후배양용기에담긴가시오가피배지부피가 6% 가되도록적당한압력으로눌러주고배양용기뚜껑으로밀폐시킨후 autoclave(jeio tech) 에서 121 C, 4분간멸균을실시한다음가시오가피배지를 25 C까지급랭시켜천연배지로사용하였다. 가시오가피- 영지버섯발효물을위한천연배지에영지버섯종균을 9% 씩접종하고 28 C에서 14일간배양하였으며, 가시오가피-상황버섯발효물을위한천연배지에상황버섯종균을 9% 씩접종하고 28 C에서 3일간배양하였다. 가시오가피-영지버섯발효물과가시오가피-상황버섯발 효물을 6 C에서건조하여열수추출한후, 동결건조하여시료로사용하였다. 또한두시료에대해지표성분인 eleutheroside B, eleutheroside E와 β-glucan의함량을분석하였다. DL-Ethionine 과 ethanol 지방간모델유발 5주령 Sprague-Dawley(SD) rats 수컷을 ( 주 ) 대한바이오링크 (Eumsung, Korea) 에서공급받았고, 입수동물은 1주일간동물실에서순화시킨후시험에사용하였다. 사육상자당 2수의 rats를사육하였고, 사육환경은자동환경조절장치로다음과같이조절하였다 ( 온도 : 22±3 C, 상대습도 : ±1%, 조도 : 2~3 Lux, 명암주기 : 12시간점등 / 12 시간소등, 조명시간 : 8시 ~2시 ). 실험동물을 1개의정상시험군 (normal: 지방간비유발 ), 1개의음성대조군 (control: ethionine or ethanol), 1개의양성대조군 (ethionine or ethanol, ursodeoxycholic acid(sigma-aldrich, St. Louis, MO, USA) 3 mg/kg 투여 ), 3개의 FM-5111 투여시험군 (ethionine or ethanol, mg/kg, FM-5111- M 1 mg/kg, 3 mg/kg), 3개의 FM-5131 투여시험군 (ethionine or ethanol, mg/kg, 1 mg/kg, 3 mg/kg) 으로설정하였고각군당 8수의 rats를공시하였다 (Table 1). DL-Ethionine 지방간모델에서의가시오가피발효물효능평가를위해시험물질인 FM-5111과 FM-5131을 DLethionine(Sigma-Aldrich) 투여일과투여하루전후에오전, 오후두번씩총 6회에걸쳐위에서언급한농도로경구투여하였으며, ethionine은생리식염수에 2%(w/v) 로녹여 2 mg/kg으로경구투여하였다. Ethanol(Duksan, Seoul, Korea) 지방간모델에서의가시오가피발효물효능평가를위해 3% ethanol을 1 ml/ kg으로오전, 오후같은시각에매일 2회에걸쳐 28일동안경구투여하였으며, 시험물질은 ethanol 투여 15일째부터 14일동안위에서언급한농도로경구투여하였다 (Table 1). 모든동물실험은충북대학교동물실험윤리위원회 ( 승인번호 : CBNUA-428-12-2) 의승인하에이루어졌다. 지방간모델의체중측정및혈액생화학적분석 Ethionine 지방간모델의체중은매일한번씩, ethanol 지방간모델의체중은매주 1회일정한시간에동물용체중계를이용하여측정하였다. 시험이종료된후시험동물을 ethyl ether(duksan) 로마취하여복부대동맥으로부터채혈하였다. 혈액은원심분리 (3, rpm, 15분 ) 한후혈청을회수하여혈청자동분석기 (Hitachi76, Hitachi, Tokyo, Japan) 를이용하여 aspartate aminotransferase(ast) 와 alanine aminotransferase (ALT) 를측정하였다.
42 조주현 박인재 최수영 백순옥 김충식 Table 1. Experimental groups in the study Group Dose (mg/kg) Ethionine-induced fatty liver model Ethanol-induced fatty liver model Induction/ Duration of study (day) Induction/ Duration of study (day) non-induction/3 non-induction/28 ethionine (2 mg/kg)/3 3% ethanol (1 ml/kg)/28 3 ethionine (2 mg/kg)/3 3% ethanol (1 ml/kg)/28 ethionine (2 mg/kg)/3 3% ethanol (1 ml/kg)/28 FM- 1 ethionine (2 mg/kg)/3 3% ethanol (1 ml/kg)/28 5111 3 ethionine (2 mg/kg)/3 3% ethanol (1 ml/kg)/28 FM- 5131 1 3 ethionine (2 mg/kg)/3 ethionine (2 mg/kg)/3 ethionine (2 mg/kg)/3 3% ethanol (1 ml/kg)/28 3% ethanol (1 ml/kg)/28 3% ethanol (1 ml/kg)/28 : saline 1 ml/kg, : fatty liver model, UCDA: fatty liver model+ursodeoxycholic acid 3 mg/kg, FM-5111: fatty liver model+fm-5111 (, 1, 3 mg/kg), FM-5131: fatty liver model+fm-5131 (, 1, 3 mg/kg). 간지질분석시험종료후시험동물의간을적출하여무게를측정하고다음시험에사용할때까지 -7 C에보관하였다. 냉동된간을 4 C에서 O/N 해동하여차가운 1.15% KCl(Sigma- Aldrich) 용액으로 1%(w/v) 가되도록잘라 homogenizer (X52, Finemech, Portola Valley, CA, USA) 로균질화하였다. 3, rpm, 15 min으로원심분리후상층액을얻어간지질분석에사용하였다. 총지질분석은 Frings와 Dunn(25) 의방법에따라상층액에 H 2SO 4(Sigma-Aldrich) 를가해끓는물에 1분간가온한후얼음물에냉각시켜 phospho-vanillin 용액을가하여 37 C에서 15분간반응시키고상온에서 5분간냉각하였다. 이반응액을 spectrophotometer(uv 161, Shimadzu, Kyoto, Japan) 를이용하여 54 nm로흡광도를측정하고, olive oil(sigma-aldrich) 을 working standard solution으로사용하여지질의양을정량하였다. 중성지방분석은 Uchiyama와 Mihara(26) 의방법에따라 1.15% KCl 용액으로 1%(w/v) 가되도록잘라균질화한후, 원심분리하여얻어진상층액을 Cleantech TG-S(Asanparm, Seoul, Korea) 를이용하여분석하였다. 통계분석실험결과는평균과표준편차로나타내었으며 SPSS program(spss 12., SPSS Inc., Chicago, IL, USA) 을이용하여일원배치분산분석 (one-way ANOVA) 을실시하였으며, 유의성이관찰되면대조군과유의차가있는시험군을확인하기위해 Dunnett's t-test의다중검정을실시하였다. 결과및고찰가시오가피발효물의지표성분함량분석지방간모델에서간기능개선효능평가에사용된시료인 FM-5111, FM5131의 eleutheroside B, E와 β-glucan의함량을분석한결과 eleutheroside B의경우 FM-5111은. mg/g, FM5131은.28 mg/g으로분석되었으며, Table 2. Eleutheroside B, E and β-glucan contents in extracts of Acanthopanax senticosus-fermented mushroom Sample FM-5111 FM-5131 Eleutheroside (mg/g) B E.±.3.28±.1.64±.11.74±.64 β-glucan (%, w/w) 4.47±.14 4.15±.6 FM-5111: water extracts of Acanthopanax senticosus-fermented Ganoderma lucidum. FM-5131: water extracts of Acanthopanax senticosus-fermented Phellnus linteus. eleutheroside E의경우 FM-5111은.64 mg/g, FM5131 은.74 mg/g으로분석되었다. 또한 β-glucan 함량의경우 FM-5111은 4.47% 로측정되었으며, FM-5131은 4.15 % 로분석되었다 (Table 2). 지방간모델의체중및혈액생화학적분석체중측정결과전체시험기간에걸쳐 ethionine 및 ethanol로유발한지방간모델에서음성대조군 (control) 과비교하여양성대조군및시험물질투여군에서통계적으로유의성있는변화는관찰되지않았다 (Table 3). 이러한결과는지방간모델에서시험물질투여가시험동물의생육에부정적인영향을주고있지않는것으로판단된다. Ethionine으로유발한지방간모델에서의혈액으로부터 AST와 ALT 수치를분석한결과 AST와 ALT 모두간에존재하는효소로간손상시혈액으로유리되어간손상의지표로서사용된다. Ethionine으로지방간이유도된 control군은 normal군에비하여모두수치가증가하였다. 특히 AST는,, 군에서 control과비교하여유의적으로감소하였다 (Fig. 1A). ALT 는모든시험군에서감소하였으나대조군과비교하여시험물질투여군에서유의적으로감소하지않았다 (Fig. 1B). Ethanol로유발한지방간모델에서의혈액으로부터 AST 와 ALT 수치를분석한결과 ethanol로지방간이유도된 control군은 normal군에비하여모두수치가증가하였으며, 시험물질투여군중,, FM- 5131-H 군에서 control과비교하여 AST의수치가유의적
지방간모델에서가시오가피발효물의간기능개선효과 43 으로감소하였다 (Fig. 2A). ALT는대조군과비교하여시험물질투여군, 양성대조군모두에서유의적으로감소하지않았다 (Fig. 2B). 알코올성간손상 (27), echovirus의감염 (28), 대사성질환 (27) 에서는 AST 수치가 ALT 수치에비해상승이더두드러진다. 따라서본연구에서의 ALT 수치가유의성이없게나타난이유는 ethionine과 ethanol에의해유발된지방간모델에서의간손상이 ALT 수치가증가하기이전에일어났기때문으로사료된다. 이러한결과로볼때 FM-5111, FM-5131은 ethionine 과 ethanol에의해유발된지방간모델에서간손상에대한예방및개선효능을갖는것으로사료된다. 지방간모델의간내총지질분석 Ethionine 지방간모델에서 control군의간내총지질량은간 g당 65.56 mg으로 normal군 31.1 mg에비해총지질량이 2배이상증가되었으며, 시험물질투여군의간내총지질량은전체적으로감소하는경향을보였다. 특히,,, 군에서총지질량이유의적으로감소하였다 (Fig. 3A). 이결과에서보면시험물질투여군의간내총지질량이양성대조군인 투여군보다더낮아진것을알수있다. Ethanol 지방간모델에서 control군은 normal군에비해간내총지질량이증가하였다. 를투여한양성대조군의간내총지질량은감소하였으며, 모든시험물질투여군에서총지질량은유의적으로현저히감소하였고 (Fig. 3B), 시험물질투여군의총지질량은양성대조군보다더감소하였다. 또한시험물질투여군에서총지질량이감소한것은시험물질투여군의간내인지질이나지방산의양이감소한것으로사료된다. 이러한결과로볼때, ethionine 또는 ethanol 지방간모델에서 FM-5111과 FM-5131은간내지질의축적을예방하는효능을갖는것으로판단된다. 그리고이러한효능은 ethionine 지방간모델보다 ethanol 지방간모델에서더욱두드러지게나타나고있다. 지방간모델의간내중성지방분석 Ethionine 지방간모델에서 control군의간조직내중성지방함유량은간 g당 52.28 mg으로 normal군 17.89 mg에비하여약 3배가량증가하였으며,, FM-5111- H,, 군에서중성지방함유량이유의적으로감소하였다 (Fig. 4A). 시험물질투여군의중성지방함유량감소정도는양성대조군인 UCDA 투여군과비슷한정도를보이고있다. Ethanol 지방간모델에서 control군은 normal군에비해간내중성지방함유량이증가하였다. 를투여한양성대조군의간내중성지방함유량은감소하였으며, FM- 5111-L,,,, FM- 5131-H 군에서중성지방함유량은유의적으로감소하였고 (Fig. 4B), 시험물질투여군의중성지방감소정도는 normal
44 조주현 박인재 최수영 백순옥 김충식 3 6 2 AST (U/L). 2 1 1 ALT (U/L). 4 3 2 1 Fig. 1. Level of AST and ALT in ethionine-induced fatty liver model. AST and ALT in sera after 3 days of administration of experimental materials., saline 1 ml/kg;, ethionine 2 mg/kg; UCDA, ethionine 2 mg/kg+ursodeoxycholic acid 3 mg/kg;, ethionine 2 mg/kg+fm-5111 mg/kg;, ethionine 2 mg/kg+fm-5111 1 mg/kg;, ethionine 2 mg/kg+fm-5111 3 mg/kg;, ethionine 2 mg/kg+fm-5131 mg/kg; FM- 5131-M, ethionine 2 mg/kg+fm-5131 1 mg/kg;, ethionine 2 mg/kg+fm-5131 3 mg/kg. Data are presented as means±sd. P<.5; Compared to control. 3 3 7 6 AST (U/L). 2 2 1 1 ALT (U/L). 4 3 2 1 Fig. 2. Level of AST and ALT in ethanol-induced fatty liver model. AST and ALT in sera after 14 days of administration of experimental materials., saline 1 ml/kg;, 3% ethanol 1 ml/kg; UCDA, 3% ethanol 1 ml/ kg+ursodeoxycholic acid 3 mg/kg;, 3% ethanol 1 ml/kg+fm-5111 mg/kg;, 3% ethanol 1 ml/kg+ FM-5111 1 mg/kg;, 3% ethanol 1 ml/kg+fm-5111 3 mg/kg;, 3% ethanol 1 ml/kg+fm-5131 mg/kg;, 3% ethanol 1 ml/kg+fm-5131 1 mg/kg;, 3% ethanol 1 ml/kg+fm-5131 3 mg/kg. Data are presented as means±sd. P<.5; Compared to control. 8 8 Total lipid (mg/g liver). 7 6 4 3 2 1 Total lipid (mg/g liver). 7 6 4 3 2 1 Fig. 3. Contents of total lipid in liver in ethionine-induced and ethanol-induced fatty liver model. Total lipid in liver in ethionine-induced fatty acid model after 3 days of administration of experimental materials. Total lipid in liver in ethanol-induced fatty acid model after 3 days of administration of experimental materials., saline 1 ml/kg;, ethionine 2 mg/kg or 3% ethanol 1 ml/kg; UCDA, ethionine 2 mg/kg or 3% ethanol 1 ml/kg+ursodeoxycholic acid 3 mg/kg;, ethionine 2 mg/kg or 3% ethanol 1 ml/kg+fm-5111 mg/kg;, ethionine 2 mg/kg or 3% ethanol 1 ml/ kg+fm-5111 1 mg/kg;, ethionine 2 mg/kg or 3% ethanol 1 ml/kg+fm-5111 3 mg/kg;, ethionine 2 mg/kg or 3% ethanol 1 ml/kg+fm-5131 mg/kg;, ethionine 2 mg/kg or 3% ethanol 1 ml/kg+fm-5131 1 mg/kg;, ethionine 2 mg/kg or 3% ethanol 1 ml/kg+fm-5131 3 mg/kg. Data are presented as means±sd. P<.5; Compared to control.
지방간모델에서가시오가피발효물의간기능개선효과 45 8 8 Triglyceride (mg/g liver). 7 6 4 3 2 1 Triglyceride (mg/g liver). 7 6 4 3 2 1 Fig. 4. Contents of triglyceride in liver in ethionine-induced and ethanol-induced fatty liver model. Triglyceride in liver in ethionine-induced fatty acid model after 3 days of administration of experimental materials. Triglyceride in liver in ethanol-induced fatty acid model after 3 days of administration of experimental materials., saline 1 ml/kg;, ethionine 2 mg/kg or 3% ethanol 1 ml/kg; UCDA, ethionine 2 mg/kg or 3% ethanol 1 ml/kg+ursodeoxycholic acid 3 mg/kg;, ethionine 2 mg/kg or 3% ethanol 1 ml/kg+fm-5111 mg/kg;, ethionine 2 mg/kg or 3% ethanol 1 ml/kg+fm-5111 1 mg/kg;, ethionine 2 mg/kg or 3% ethanol 1 ml/kg+fm-5111 3 mg/kg;, ethionine 2 mg/kg or 3% ethanol 1 ml/kg+fm-5131 mg/kg;, ethionine 2 mg/kg or 3% ethanol 1 ml/kg+fm-5131 1 mg/kg;, ethionine 2 mg/kg or 3% ethanol 1 ml/kg+fm-5131 3 mg/kg. Data are presented as means±sd. P<.5; Compared to control. 군의감소수준으로감소하였다. 간에서에탄올대사시 alcohol dehydrogenase(adh), acetaldehyde dehydrogenase(aldh) 효소들을통해알코올에서유리된수소이온이보효소인 NAD(P) + 로이송되어 NADH가형성되며, 이때간세포내에 NAD(P) + 의소모가증가되어 NADH가너무많아지면서 NAD(P) + /NADH 비율의불균형이유도되어 (29) 세포독성이유발된다 (3). 이로인하여 NAD(P) + 는고갈되고, NADH가과잉생성되게된다. 또한과잉생성된수소가에너지원으로사용되어지방산산화 (β-oxidation) 를감소시켜중성지방 (triglyceride) 의축적 (31), citric acid cycle의 activity 감소를초래한다. 따라서 FM-5111과 FM-5131은아마도불균형한 NAD(P) + /NAD(P)H + 의농도를보완하여중성지방의축적을억제하는효과가있을것으로추정된다. 이러한결과들은 FM-5111과 FM-5131이 ethionine과 ethanol 지방간모델에서간내중성지방의축적을예방하는데효능을갖는것을보여주고있으며, 그효능은양성대조군인 UCDA와유사함을알수있었다. 또한 FM-5111과 FM-5131의이러한효능은 ethionine 지방간모델과 ethanol 지방간모델에서유사한경향을보이고있다. 따라서 FM-5111과 FM-5131은비알코올성지방간과알코올성지방간형성을억제하는효능을갖는것으로사료된다. 요약본연구에서는두종류의가시오가피발효물추출물 (FM- 5111, FM-5131) 에대한지방간예방및개선효능을검토하였다. 그결과 FM-5111, FM-5131 모두 ethionine과 ethanol 지방간모델에서간손상의지표인 AST의수치를감소시키며, 간내총지질량과중성지방함유량을감소시키는효능을보이고있다. 특히간내총지질량과중성지방 함유량의감소정도로보았을때, ethanol 지방간모델에서더욱두드러진효능을보이고있다. 따라서 FM-5111과 FM-5131은비알코올성지방간형성을예방하고알코올에의해형성된지방간을개선하는효능을가지고있으며, 비알코올성지방간과알코올성지방간모델에서간손상등을억제하는것으로판단된다. 감사의글 본논문은농림수산식품기술기획평가원고부가가치식품기술개발사업 ( 과제번호 : 11128) 의지원에의해이루어진것임. REFERENCES 1. Salgado Júnior W, Santos JS, Sankarankutty AK, de Castro e Silva O. 26. Nonalcoholic fatty liver disease and obesity. Acta Cir Bras 21 (suppl. 1): 72-78. 2. Younossi ZM. 1999. Nonalcoholic fatty liver disease. Curr Gastroenterol Rep 1: 57-62. 3. Stewart S, Jones D, Day CP. 21. Alcoholic liver disease: new insights into mechanisms and preventative strategies. Trends Mol Med 7: 48-413. 4. Purohit V, Russo D, Coates PM. 24. Role of fatty liver, dietary fatty acid supplements, and obesity in the progression of alcoholic liver disease: introduction and summary of the symposium. Alcohol 34: 3-8. 5. Caldwell SH, Harris DM, Patrie JT, Hespenheide EE. 22. Is NASH underdiagnosed among African Americans? Am J Gastroenterol 97: 1496-1. 6. Lieber CS. 24. Alcoholic fatty liver: its pathogenesis and mechanism of progression to inflammation and fibrosis. Alcohol 34: 9-19. 7. Lakshman MR. 24. Some novel insights into the pathogenesis of alcoholic steatosis. Alcohol 34: 45-48.
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